5-Membered cyclic carbamate

Both, five- and six-membered cyclic carbamates have been synthesized by the reaction of 2-(l-haloalkyl)-oxiranes with C02 and primary aliphatic amines [81]. Notably, 5-substituted 2-oxazolidinones have been prepared in good yield (51-94%) by reacting 2-aminomethyloxiranes with C02 (0.1 MPa), in MeOH, at room temperature [82]. 

A versatile ring opening of five- and six-membered cyclic carbamates yielding acyclic, V-protected 1,2- and 1,3-amino alcohols involves protection with the AT-tert-butoxycarbonyl group, followed by cleavage with cesium carbonate in methanol13. 

Homoallylic carbamates also cyclize smoothly with sodium hydride to yield 6-membered cyclic carbamates with high l,3-s>v asymmetric induction70-147. The presence of a Z double bond also improves the stereoselectivity to a large extent. 

NH3R) derived from a primary amine, in the presence of C02, perhydrooxazin-2-ones (six-membered cyclic carbamates) are isolated (Scheme 18) <93H(35)623>. 

Several synthetic methods were presented in Sections 4.3.2, 4.3.3, and 4.3.4, in which five-membered cyclic carbamates (oxazolidin-2-ones), cyclic carbonates (1,3-dioxolan-2-ones), and cyclic ureas (imidazolidin-2-ones), respectively, were constructed. General reviews of the synthesis and chemistry of 2-oxazolidinones and thiazolidin-2-ones [363, 364], reporting the reactions of N,0- and N,S-l,2-binu-cleophUic substrates with various carbonylating agents, are available. 

Although, in the past the ROP of cyclic carbamates has been rarely mentioned, it has been the subject of more detailed study more recently [56]. The six-mem-bered trimethylene carbamate was the first cychc carbamate to be successfuUy ring-opened by employing trifluoromethane sulfonate as the catalyst. Only the unsubshtuted six- and seven-membered cyclic carbamates (Scheme 5.13) can be ring-opening polymerized [68-70]. The cationic ROP has subsequently been used in block copolymerizations starting from tehahydrofuran (THF) to yield either AB- or ABA-type polymers. 

When sulfamate esters 114 are used as substrates, six-membered-ring formation is favored, and results in the selective formation of 1,2,3-oxathiazinane-2,2-dioxide heterocycles 115.251 Nevertheless, five-membered cyclic sulfamidates could be obtained when no alternative cyclization was possible. 1,3-Amino alcohols and related /2-amino acids are thus readily accessible from the same simple alcohols 113 by converting them into sulfamates 114 (Equation (90)). Furthermore, in comparison to the carbamate reaction (Scheme 9), the sulfamate substrates have... 

Theoretical evidence for the thermal decomposition mechanism for ethyl oxam-ate, ethyl oxanilate, and ethyl A,A-dimethyl oxamate have been provided.27 Ethyl oxamate and ethyl oxanilate undergo rapid decarbonylation to give the corresponding carbamates. Ethyl A,lV-dimethyloxamate elimination reaction yields in one step, through a six-membered cyclic transition state, dimethyloxamic acid and ethylene gas. 

E2 elimination reactions occur preferentially when the leaving groups are in an anti copla-nar arrangement in the transition state. However, there are a few thermal, unimolecular sy -eliminations that produce alkenes. For example, pyrolysis of several closely related amine oxides, sulfoxides, selenoxides, acetates, benzoates, carbonates, carbamates and thio-carbamates gives alkenes on heating (Scheme 4.10). The syn character of these eliminations is enforced by a five- or six-membered cyclic transition states by which they take place. 

Let us now consider to what extent the previous reaction of phosgene with a-amino acid can be applied to (5-amino acids to yield six membered cyclic 0-acyl carbamates. 

H-3,1-Benzoxazine-2,4(1 H)-dione known as isatoic anhydride (VI) is the most popular six membered cyclic O-acyl carbamate. The synthesis of isatoic anhydride by ring closure of anthranilic acid with phosgene is well described (Ref. 250). However, we have developed an... 

N-(l-Alkoxyalkyl)-aniides or -carbamates (2 X = OR), most frequently used as stable precursors for A -acyliminium ions, are usually prepared by one of the following routes (equations 7-13). For five- or six-membered cyclic cases a simple acid-catalyzed solvolysis of the hydroxy compound provides the alk-oxy derivative (equation 7). A silicon-assisted approach involves the TMSOTf-catalyzed reaction of bis(trimethylsilyl)formamide with aldehydes (equation 8). /V-(l-Trimethylsilyloxyalkyl)formamides are thus formed in good yields, which on TMSOTf-catalyzed solvolysis lead to the /V-( 1-alkoxyalkyl)form-amides. A third method is based on the NaBH4 reduction of imidates (equation 9), and has proved useful for a total synthesis of the insect poison pederine. Addition of reactive acid derivatives to imines constitutes another method (equations 10 and 11). Acylation with acid chlorides followed by treatment with ethanol in the presence of base leads to N-(l-alkoxyalkyl)amides. A one-step protocol using diethyl dicarbonate provides the corresponding carbamates. 2... 

Various V-methyl and 0-methyl derivatives (4"-, 6-, 11-, and 12-) of 37 were prepared and evaluated for their antibacterial activity. 6-O-Methyl AZM (56a) (Fig. 10) was slightly less active than AZM, while 11-0-methyl AZM (56b) exhibited remarkably increased antibacterial activity [72-74]. (Structure of 6-0 methyl AZM was later revised to 12-O-methyl AZM [73, 74].) 9a-V, 11-Cyclic carbamate azalide (57), 8a-V-azalides (58), and 14-membered azalide (59) (Fig. 10) are interesting in view of their structure-activity relationship compared with 19, although they generally exhibited the same or lower activity compared with AZM (19) [75-78]. 

The peptide-based phosphine ligand 105 was identified from a polymer-supported phosphine library of 75 members [154]. Enantioposition-selective desymmetrization of the meso-cyclopentenediol derivative 100 was promoted by a palladium complex of 105 to afford the cyclic carbamate 101 with 76% ee. This result demonstrated that the combinatorial approach is effective in the lead-generation stage of stereoselective catalyst development [155, 156]. The resin-supported palladium complex of Ac-D-Phg-Pro-D-Val-Pps-D-Leu-NH resin 106, which has also been developed through the combinatorial approach. 

The effect of the solvent on the product selectivity for the rhodium-catalyzed cyclization of an allylamine under a CO/H2 atmosphere (Scheme 70) is such that carbonylation in conventional organic solvents forms a cyclic amide 41, whereas the reaction in SCCO2 preferentially produces reduced five-membered cyclic amine 40. In SCCO2, the amino group of the starting material is transformed to the carbamic... 

In 1992 Murahashi, Hosokawa, and co-workers described the anti-Markovnikov oxidative addition of amides and carbamates to electron-deficient olefins by applying a palladium and copper cooperative catalysis under oxygen atmosphere [41]. The proposed mechanism involved a ff-bonded palladium(II) intermediate resulting from the addition of the nucleophile to the olefin, and subsequent ) -palladium hydride elimination to yield the functionalized alkene. Interestingly, both lactams and cyclic carbamates gave predominantly the corresponding E-enamide derivatives. Acyclic amides, conversely, afforded ElZ mixtures of products. The addition of a catalytic amount (5 mol%) of hexamethylphosphoric triamide (HMPA) was found notably beneficial for the reaction of 5-membered lactams and reduced the reaction time of such particular oxidative amidations (Scheme 2). 

Examples of the preparation of cyclopropanes by intramolecular nucleophilic substitution are illustrated in Scheme9.17. The first example is a synthesis of [l.l.ljpro-pellane, which yields the product in acceptable yields, despite the high strain and poor stability of this compound [66]. The second and third examples illustrate the remarkable ease with which 3-halopropyl ketones cyclize to yield cyclopropanes instead of cyclic, five-membered enol ethers or ketones. Similarly, carbamates of 2-haloethylglycine esters do not undergo intramolecular N- or O-alkylation on treatment with bases, but yield cyclopropanes instead [67, 68]. Some nucleophiles can undergo Michael addition to 3-halomethyl acrylates faster than direct Sn2 reaction, to yield cyclopropanes by cyclization of the intermediate enolates (fourth example, Scheme9.17) [69]. 

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